diff --git a/biology/minimap2/Makefile b/biology/minimap2/Makefile
index 8f99d646431d..52b9b669654a 100644
--- a/biology/minimap2/Makefile
+++ b/biology/minimap2/Makefile
@@ -1,24 +1,24 @@
-PORTNAME=	minimap2
+PORTNAME=		minimap2
 DISTVERSIONPREFIX=	v
-DISTVERSION=	2.22
-CATEGORIES=	biology
+DISTVERSION=		2.23
+CATEGORIES=		biology
 
 MAINTAINER=	jwb@FreeBSD.org
 COMMENT=	Pairwise aligner for genomic and spliced nucleotide sequences
 
 LICENSE=	MIT
 LICENSE_FILE=	${WRKSRC}/LICENSE.txt
 
-ONLY_FOR_ARCHS=	amd64 i386
-ONLY_FOR_ARCHS_REASON=	uses hard-coded SSE instructions
+BUILD_DEPENDS=	simde>0:devel/simde
 
-USES=		gmake
+USES=		gmake localbase
 USE_GITHUB=	yes
 
 GH_ACCOUNT=	lh3
 
-MAKE_ARGS+=	CFLAGS+=-Wextra
 ALL_TARGET=	extra
 INSTALL_TARGET=	install-strip
 
+MAKEFILE=	Makefile.simde
+
 .include <bsd.port.mk>
diff --git a/biology/minimap2/distinfo b/biology/minimap2/distinfo
index e52728d52312..8488018ac682 100644
--- a/biology/minimap2/distinfo
+++ b/biology/minimap2/distinfo
@@ -1,3 +1,3 @@
-TIMESTAMP = 1629640993
-SHA256 (lh3-minimap2-v2.22_GH0.tar.gz) = b625a7580d9b5996f2553ee90ffcec84870bd9b88c009c9d71e8c1c648c53ed6
-SIZE (lh3-minimap2-v2.22_GH0.tar.gz) = 251821
+TIMESTAMP = 1638198281
+SHA256 (lh3-minimap2-v2.23_GH0.tar.gz) = 1837465234bfec0fc8acaa3bdd371dfc57cf56137f7e6b8c723dcbed2f03f144
+SIZE (lh3-minimap2-v2.23_GH0.tar.gz) = 252484
diff --git a/biology/minimap2/files/patch-Makefile b/biology/minimap2/files/patch-Makefile
deleted file mode 100644
index 79c9c3617b38..000000000000
--- a/biology/minimap2/files/patch-Makefile
+++ /dev/null
@@ -1,61 +0,0 @@
---- Makefile.orig	2021-05-27 19:26:04 UTC
-+++ Makefile
-@@ -1,5 +1,9 @@
--CFLAGS=		-g -Wall -O2 -Wc++-compat #-Wextra
--CPPFLAGS=	-DHAVE_KALLOC
-+
-+# Makefile patches rejected by upstream
-+
-+CFLAGS?=	-g -Wall -O2
-+CFLAGS+=	-Wc++-compat #-Wextra
-+CPPFLAGS?=	-DHAVE_KALLOC
- INCLUDES=
- OBJS=		kthread.o kalloc.o misc.o bseq.o sketch.o sdust.o options.o index.o \
- 			lchain.o align.o hit.o seed.o map.o format.o pe.o esterr.o splitidx.o \
-@@ -8,6 +12,15 @@ PROG=		minimap2
- PROG_EXTRA=	sdust minimap2-lite
- LIBS=		-lm -lz -lpthread
- 
-+PREFIX?=	/usr/local
-+MAN1DIR?=	${PREFIX}/man/man1
-+DATADIR?=	${PREFIX}/share/minimap2
-+
-+MKDIR?=		mkdir
-+CP?=		cp
-+INSTALL?=	install
-+STRIP?=		strip
-+
- ifeq ($(arm_neon),) # if arm_neon is not defined
- ifeq ($(sse2only),) # if sse2only is not defined
- 	OBJS+=ksw2_extz2_sse41.o ksw2_extd2_sse41.o ksw2_exts2_sse41.o ksw2_extz2_sse2.o ksw2_extd2_sse2.o ksw2_exts2_sse2.o ksw2_dispatch.o
-@@ -34,7 +47,7 @@ ifneq ($(tsan),)
- 	LIBS+=-fsanitize=thread
- endif
- 
--.PHONY:all extra clean depend
-+.PHONY:all extra install clean depend
- .SUFFIXES:.c .o
- 
- .c.o:
-@@ -96,6 +109,21 @@ ksw2_exts2_neon.o:ksw2_exts2_sse.c ksw2.h kalloc.h
- 		$(CC) -c $(CFLAGS) $(CPPFLAGS) -DKSW_SSE2_ONLY -D__SSE2__ $(INCLUDES) $< -o $@
- 
- # other non-file targets
-+
-+install: all
-+	${MKDIR} -p ${DESTDIR}${PREFIX}/bin
-+	${MKDIR} -p ${DESTDIR}${MAN1DIR}
-+	${MKDIR} -p ${DESTDIR}${DATADIR}
-+	${INSTALL} -c minimap2 ${DESTDIR}${PREFIX}/bin
-+	${INSTALL} -c minimap2-lite ${DESTDIR}${PREFIX}/bin
-+	${INSTALL} -c sdust ${DESTDIR}${PREFIX}/bin
-+	${INSTALL} -c minimap2.1 ${DESTDIR}${MAN1DIR}
-+	${CP} -R test ${DESTDIR}${DATADIR}
-+
-+install-strip: install
-+	${STRIP} ${DESTDIR}${PREFIX}/bin/minimap2
-+	${STRIP} ${DESTDIR}${PREFIX}/bin/minimap2-lite
-+	${STRIP} ${DESTDIR}${PREFIX}/bin/sdust
- 
- clean:
- 		rm -fr gmon.out *.o a.out $(PROG) $(PROG_EXTRA) *~ *.a *.dSYM build dist mappy*.so mappy.c python/mappy.c mappy.egg*
diff --git a/biology/minimap2/files/patch-Makefile.simde b/biology/minimap2/files/patch-Makefile.simde
new file mode 100644
index 000000000000..8a85b5257ffc
--- /dev/null
+++ b/biology/minimap2/files/patch-Makefile.simde
@@ -0,0 +1,82 @@
+--- Makefile.simde.orig	2021-11-18 22:11:48 UTC
++++ Makefile.simde
+@@ -1,13 +1,26 @@
+-CFLAGS=		-g -Wall -O2 -Wc++-compat #-Wextra
+-CPPFLAGS=	-DHAVE_KALLOC -DUSE_SIMDE -DSIMDE_ENABLE_NATIVE_ALIASES
+-INCLUDES=	-Ilib/simde
+-OBJS=		kthread.o kalloc.o misc.o bseq.o sketch.o sdust.o options.o index.o lchain.o align.o hit.o map.o format.o pe.o seed.o esterr.o splitidx.o \
+-			ksw2_extz2_simde.o ksw2_extd2_simde.o ksw2_exts2_simde.o ksw2_ll_simde.o
++
++# Makefile patches rejected by upstream
++
++CFLAGS?=	-g -Wall -O2
++CFLAGS+=	-Wc++-compat -DUSE_SIMDE -DSIMDE_ENABLE_NATIVE_ALIASES -D__SSE2__
++CPPFLAGS?=	-DHAVE_KALLOC
++OBJS=		kthread.o kalloc.o misc.o bseq.o sketch.o sdust.o options.o \
++		index.o lchain.o align.o hit.o map.o format.o pe.o seed.o \
++		esterr.o splitidx.o ksw2_extz2_simde.o ksw2_extd2_simde.o \
++		ksw2_exts2_simde.o ksw2_ll_simde.o
+ PROG=		minimap2
+ PROG_EXTRA=	sdust minimap2-lite
+ LIBS=		-lm -lz -lpthread
+ 
++PREFIX?=	/usr/local
++MAN1DIR?=	${PREFIX}/man/man1
++DATADIR?=	${PREFIX}/share/minimap2
+ 
++MKDIR?=		mkdir
++CP?=		cp	
++INSTALL?=	install
++STRIP?=		strip
++
+ ifneq ($(arm_neon),) # if arm_neon is defined
+ ifeq ($(aarch64),)   #if aarch64 is not defined
+ 	CFLAGS+=-D_FILE_OFFSET_BITS=64 -mfpu=neon -fsigned-char
+@@ -26,7 +39,7 @@ ifneq ($(tsan),)
+ 	LIBS+=-fsanitize=thread
+ endif
+ 
+-.PHONY:all extra clean depend
++.PHONY:all extra install install-strip clean depend
+ .SUFFIXES:.c .o
+ 
+ .c.o:
+@@ -49,18 +62,34 @@ sdust:sdust.c kalloc.o kalloc.h kdq.h kvec.h kseq.h ke
+ 		$(CC) -D_SDUST_MAIN $(CFLAGS) $< kalloc.o -o $@ -lz
+ 
+ ksw2_ll_simde.o:ksw2_ll_sse.c ksw2.h kalloc.h
+-		$(CC) -c $(CFLAGS) -msse2 $(CPPFLAGS) $(INCLUDES) $< -o $@
++		$(CC) -c $(CFLAGS) $(CPPFLAGS) $(INCLUDES) $< -o $@
+ 
+ ksw2_extz2_simde.o:ksw2_extz2_sse.c ksw2.h kalloc.h
+-		$(CC) -c $(CFLAGS) -msse4.1 $(CPPFLAGS) $(INCLUDES) $< -o $@
++		$(CC) -c $(CFLAGS) $(CPPFLAGS) $(INCLUDES) $< -o $@
+ 
+ ksw2_extd2_simde.o:ksw2_extd2_sse.c ksw2.h kalloc.h
+-		$(CC) -c $(CFLAGS) -msse4.1 $(CPPFLAGS) $(INCLUDES) $< -o $@
++		$(CC) -c $(CFLAGS) $(CPPFLAGS) $(INCLUDES) $< -o $@
+ 
+ ksw2_exts2_simde.o:ksw2_exts2_sse.c ksw2.h kalloc.h
+-		$(CC) -c $(CFLAGS) -msse4.1 $(CPPFLAGS) $(INCLUDES) $< -o $@
++		$(CC) -c $(CFLAGS) $(CPPFLAGS) $(INCLUDES) $< -o $@
+ 
+ # other non-file targets
++
++
++install: all
++	${MKDIR} -p ${DESTDIR}${PREFIX}/bin
++	${MKDIR} -p ${DESTDIR}${MAN1DIR}
++	${MKDIR} -p ${DESTDIR}${DATADIR}
++	${INSTALL} -c minimap2 ${DESTDIR}${PREFIX}/bin
++	${INSTALL} -c minimap2-lite ${DESTDIR}${PREFIX}/bin
++	${INSTALL} -c sdust ${DESTDIR}${PREFIX}/bin
++	${INSTALL} -c minimap2.1 ${DESTDIR}${MAN1DIR}
++	${CP} -R test ${DESTDIR}${DATADIR}
++
++install-strip: install
++	${STRIP} ${DESTDIR}${PREFIX}/bin/minimap2
++	${STRIP} ${DESTDIR}${PREFIX}/bin/minimap2-lite
++	${STRIP} ${DESTDIR}${PREFIX}/bin/sdust
+ 
+ clean:
+ 		rm -fr gmon.out *.o a.out $(PROG) $(PROG_EXTRA) *~ *.a *.dSYM build dist mappy*.so mappy.c python/mappy.c mappy.egg*
diff --git a/biology/minimap2/files/patch-example.c b/biology/minimap2/files/patch-example.c
new file mode 100644
index 000000000000..aaa89ec16f41
--- /dev/null
+++ b/biology/minimap2/files/patch-example.c
@@ -0,0 +1,11 @@
+--- example.c.orig	2021-11-30 15:26:24 UTC
++++ example.c
+@@ -44,7 +44,7 @@ int main(int argc, char *argv[])
+ 			for (j = 0; j < n_reg; ++j) { // traverse hits and print them out
+ 				mm_reg1_t *r = &reg[j];
+ 				assert(r->p); // with MM_F_CIGAR, this should not be NULL
+-				printf("%s\t%d\t%d\t%d\t%c\t", ks->name.s, ks->seq.l, r->qs, r->qe, "+-"[r->rev]);
++				printf("%s\t%zu\t%d\t%d\t%c\t", ks->name.s, ks->seq.l, r->qs, r->qe, "+-"[r->rev]);
+ 				printf("%s\t%d\t%d\t%d\t%d\t%d\t%d\tcg:Z:", mi->seq[r->rid].name, mi->seq[r->rid].len, r->rs, r->re, r->mlen, r->blen, r->mapq);
+ 				for (i = 0; i < r->p->n_cigar; ++i) // IMPORTANT: this gives the CIGAR in the aligned regions. NO soft/hard clippings!
+ 					printf("%d%c", r->p->cigar[i]>>4, MM_CIGAR_STR[r->p->cigar[i]&0xf]);